# Noradrenergic regulation of grey-matter astrocyte maturation

> **NIH NIH F30** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2021 · $38,595

## Abstract

PROJECT ABSTRACT:
Appropriate synapse formation and maturation are critical processes contributing to brain development. We now
know that synaptic connections between neurons are extensively affected by astrocytes. Astrocytes, by virtue of
their elaborate synapse-associated processes, in conjunction with secreted molecules, promote synapse
formation, enhance synapse maturation, and regulate synapse elimination. Alterations in astrocyte morphology
have repeatedly been shown to lessen the number and/or strength of excitatory synapses. However, not all
astrocytes are associated with synapses. A single grey-matter astrocyte can encompass tens of thousands of
synapses within its complex, highly branched arbor. In contrast, less-branched white-matter astrocytes are
located in regions of low synapse density. The molecular mechanisms by which astrocyte identity is specified
and maintained are largely unknown.
In a screen of molecules enriched in developing grey-matter vs. white-matter astrocytes, we identified adrenergic
receptors as preferentially enriched in the grey-matter astrocyte population. This suggests that norepinephrine
may be an important positive modulator of grey-matter astrocyte maturation. Preliminary evidence in this
proposal shows that astrocytes express the beta 1 adrenergic receptors. Stimulation of beta-adrenergic
receptors increases astrocyte primary branching in vitro, while depletion of norepinephrine or beta-adrenergic
receptors in vivo causes cortical grey-matter astrocytes to exhibit reduced morphologic complexity, along with
reduced expression of grey-matter astrocyte markers. This proposal will test the hypothesis that norepinephrine
signals through astrocytic beta-adrenergic receptors to increase morphologic complexity, which in turn increases
their capacity to support synapse formation and function. Aim 1 will use global and astrocyte-specific conditional
deletion of the beta 1 adrenergic receptor to determine whether beta-adrenergic signaling drives astrocyte
morphologic complexity and molecular identity. Aim 2 will use the same experimental models to identify the
impact of beta-adrenergic signaling on the development of cortical excitatory synapses. Data from these aims
will elucidate how norepinephrine, a ubiquitous neuromodulator dynamically altered in processes such as arousal
and stress, influences the development of grey-matter astrocytes and their ability to promote excitatory synapse
development in the cortex.

## Key facts

- **NIH application ID:** 10201437
- **Project number:** 5F30MH124367-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Marci Rosenberg
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $38,595
- **Award type:** 5
- **Project period:** 2020-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10201437

## Citation

> US National Institutes of Health, RePORTER application 10201437, Noradrenergic regulation of grey-matter astrocyte maturation (5F30MH124367-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10201437. Licensed CC0.

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